U.S. patent application number 10/212472 was filed with the patent office on 2003-02-27 for systems, methods, and compositions for achieving closure of suture sites.
This patent application is currently assigned to NeoMend, Inc.. Invention is credited to Addis, Bruce, Browne, Daniel, Cheung, David, Hnojewyj, Olexander.
Application Number | 20030040760 10/212472 |
Document ID | / |
Family ID | 31494344 |
Filed Date | 2003-02-27 |
United States Patent
Application |
20030040760 |
Kind Code |
A1 |
Hnojewyj, Olexander ; et
al. |
February 27, 2003 |
Systems, methods, and compositions for achieving closure of suture
sites
Abstract
Systems and methods employ functional instruments to close
incisions and wounds using a suture knot in combination with a
biocompatible material composition. The systems and methods are
well suited for use, for example, at a vascular puncture site
following a vascular access procedure.
Inventors: |
Hnojewyj, Olexander;
(Saratoga, CA) ; Addis, Bruce; (Redwood City,
CA) ; Browne, Daniel; (Palo Alto, CA) ;
Cheung, David; (Santa Cruz, CA) |
Correspondence
Address: |
RYAN KROMHOLZ & MANION, S.C.
Post Office Box 26618
MILWAUKEE
WI
53226
US
|
Assignee: |
NeoMend, Inc.
|
Family ID: |
31494344 |
Appl. No.: |
10/212472 |
Filed: |
August 5, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10212472 |
Aug 5, 2002 |
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10141510 |
May 8, 2002 |
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10141510 |
May 8, 2002 |
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09780843 |
Feb 9, 2001 |
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09780843 |
Feb 9, 2001 |
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09283535 |
Apr 1, 1999 |
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6458147 |
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09283535 |
Apr 1, 1999 |
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09188083 |
Nov 6, 1998 |
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6371975 |
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Current U.S.
Class: |
606/148 ;
606/213; 606/214 |
Current CPC
Class: |
A61B 17/00491 20130101;
A61B 2017/00495 20130101; A61B 2017/00637 20130101; A61B 2017/0065
20130101; A61B 17/0057 20130101; A61B 2017/00004 20130101; A61B
2017/00663 20130101; A61B 2017/00654 20130101 |
Class at
Publication: |
606/148 ;
606/213; 606/214 |
International
Class: |
A61B 017/04 |
Claims
What is claimed is:
1. A knot pusher comprising a body including a passage having a
distal end, the body being sized and configured to engage a suture
knot adjacent the distal end of the passage, and a fitting carried
by body sized and configured for introducing a liquid closure
material into the passage for discharge through the distal end
adjacent the suture knot, the liquid closure material reacting
after discharge to form a solid closure adjacent the suture
knot.
2. A knot pusher according to claim 1 wherein the body is sized and
configured for locating the suture knot in a tissue puncture
tract.
3. A knot pusher according to claim 1 wherein the body is sized and
configured for locating the suture knot adjacent a puncture site in
a blood vessel.
4. A knot pusher according to claim 1 further including a dispenser
sized and configured for coupling to the fitting, the dispenser
including at least first and second components which, upon mixing,
form the liquid closure material and the solid closure adjacent the
suture knot.
5. A knot pusher according to claim 1 wherein the passage has a
proximal end, and wherein the fitting is carried by the body
adjacent the proximal end of the passage.
6. A knot pusher according to claim 1 wherein the body comprises a
knot pusher shaft including the passage.
7. A knot pusher according to claim 6 wherein the shaft includes a
side slot communicating with the distal end of the passage to
receive a free end of the suture knot passed through the distal end
of the passage, to thereby engage the suture knot adjacent the
distal end of the passage.
8. A knot pusher according to claim 7 further including a suture
threading element sized and configured to capture the free end of
the suture knot adjacent the distal end of the passage and thread
the free end into the passage and through the side slot.
9. A knot pusher according to claim 1 wherein the body comprises an
outer sheath having an interior lumen and a knot pusher shaft that
is sized and configured for insertion through the interior lumen to
form an assembly, and wherein the passage is formed in the interior
lumen in space not occupied by the knot pusher shaft.
10. A knot pusher according to claim 9 wherein the fitting is
carried by the outer sheath.
11. A knot pusher according to claim 9 wherein the knot pusher
shaft includes an open distal end and a side slot communicating
with the open distal end to receive a free end of the suture knot
passed through the open distal end, to thereby engage the suture
knot adjacent the distal end of the passage.
12. A knot pusher according to claim 11 further including a suture
threading element sized and configured to capture the free end of
the suture knot adjacent the open distal end and thread the free
end into the open distal end and through the side slot.
13. An assembly for sealing a puncture site in a blood vessel
comprising a suture knot formed at the puncture site, and a
dispenser to discharge a liquid closure material adjacent the
suture knot, the liquid closure material reacting after discharge
to form a solid closure adjacent the suture knot.
14. An assembly according to claim 13 wherein the liquid closure
material comprises a first component including an electrophilic
polymer material having a functionality of at least three, a second
component including a nucleophilic material that, when mixed with
the first component and after discharge as a liquid, cross-links
with the first component to form the solid closure, a non-liquid,
three-dimensional barrier, and a buffer material mixed with the
second component.
15. An assembly according to claim 13 wherein the liquid closure
material comprises a first component including an electrophilic
polymer material having a functionality of at least three, a second
component including a nucleophilic material that, when mixed with
the first component within a reaction pH range of between 7 to 9
and after discharge as a liquid, cross-links with the first
component to form a non-liquid, three-dimensional barrier, and a
buffer material mixed with the second component and having a pH
within the reaction pH range.
16. An assembly according to claim 15 wherein the buffer material
includes tris-hydroxymethylaminomethane.
17. An assembly according to claim 15 wherein the buffer material
includes sodium carbonate anhydrous.
18. An assembly according to claim 13 wherein the liquid closure
material comprises a first component including poly(ethylene
glycol), poly(ethylene oxide), poly(vinyl alcohol),
poly(vinylpyrrolidinone), poly(ethyloxazoline), and poly(ethylene
glycol)-co-poly(propylene glycol) block copolymers, a second
component comprising a hydrophilic protein, and a buffer
material.
19. An assembly according to claim 18 wherein the hydrophilic
protein is selected from a group consisting essentially of serum,
serum fractions, and solutions of albumin, gelatin, antibodies,
fibrinogen, and serum proteins.
20. An assembly according to claim 18 wherein the first component
comprises a compound of the formula PEG-(DCR-CG)n, where PEG is
poly(ethylene glycol), DCR is a degradation control region, CG is a
cross-linking group, and n is equal to or greater than three.
21. An assembly according to claim 18 wherein the buffer material
includes tris-hydroxymethylaminomethane.
22. An assembly according to claim 18 wherein the buffer material
includes sodium carbonate anhydrous.
23. An assembly according to claim 13 wherein the liquid closure
material comprises a first component including a multi-armed
polymer structure, a second component comprising a hydrophilic
protein, and a buffer material.
24. An assembly according to claim 23 wherein the hydrophilic
protein comprises at least one synthetic amino acid sequence.
25. An assembly according to claim 23 wherein the hydrophilic
protein comprises recombinant or natural human serum albumin.
26. An assembly according to claim 23 wherein the hydrophilic
protein comprises human serum albumin at a concentration of about
25% or less.
27. An assembly according to claim 23 wherein the buffer material
includes tris-hydroxymethylaminomethane.
28. An assembly according to claim 23 wherein the buffer material
includes sodium carbonate anhydrous.
29. A method for sealing a suture knot comprising the steps of
forming a suture knot, and discharging a liquid closure material
adjacent the suture knot, the liquid closure material reacting
after discharge to form a solid closure adjacent the suture
knot.
30. A method according to claim 29 wherein the forming step
includes manipulating a knot pusher.
31. A method according to claim 30 wherein the discharging step
includes discharging the liquid closure material through the knot
pusher.
32. A method for sealing a puncture site in a blood vessel
comprising the steps of forming a suture knot formed at the
puncture site, and discharging a liquid closure material adjacent
the suture knot, the liquid closure material reacting after
discharge to form a solid closure adjacent the suture knot.
33. A method according to claim 32 wherein the forming step
includes manipulating a knot pusher.
34. A method according to claim 33 wherein the discharging step
includes discharging the liquid closure material through the knot
pusher.
Description
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent
application Ser. No. 10/141,510, filed May 8, 2002 and entitled
"Systems, Methods, and Compositions for Achieving Closure of
Vascular Puncture Sites," which is a continuation-in-part of U.S.
patent application Ser. No. 09/780,843, filed Feb. 9, 2001, and
entitled "Systems, Methods, and Compositions for Achieving Closure
of Vascular Puncture Sites," which is a continuation-in-part of
U.S. patent application Ser. No. 09/283,535, filed Apr. 1, 1999,
and entitled "Compositions, Systems, And Methods For Arresting or
Controlling Bleeding or Fluid Leakage in Body Tissue," which is
itself a continuation-in-part of U.S. patent application Ser. No.
09/188,083, filed Nov. 6, 1998 and entitled "Compositions, Systems,
and Methods for Creating in Situ, Chemically Cross-linked,
Mechanical Barriers," all of which are incorporated herein by
reference.
FIELD OF THE INVENTION
[0002] The invention generally relates to the systems and methods
for closing suture sites in body tissue to affect desired
therapeutic results.
BACKGROUND OF THE INVENTION
[0003] There are many therapeutic indications today that pose
problems in terms of technique, cost efficiency, or efficacy, or
combinations thereof.
[0004] For example, following an interventional procedure, such as
angioplasty or stent placement, a 5 Fr to 9 Fr arteriotomy remains.
Typically, the bleeding from the arteriotomy is controlled through
pressure applied by hand, by sandbag, or by C-clamp for at least 30
minutes. While pressure will ultimately achieve hemostasis, the
excessive use and cost of health care personnel is incongruent with
managed care goals.
[0005] Various alternative methods for sealing a vascular puncture
site have been tried. For example, devices that surgically suture
the puncture site percutaneously have been used. Suture is used
because it is perceived as providing a reliable and tight closure
of any wound where the suture can be properly placed, tied, and
tightened. Suturing is relatively straightforward in most open
surgical procedures. However, placement and tying of sutures in
closed, minimally invasive procedures, e.g., in laparoscopic or
catheter-based procedures, often require placement, tying, and
tightening of a suture knot transcutaneously through a tissue
tract. A variety of devices have been developed for the
transcutaneous placement, tying, and tightening of suture knots
through a tissue tract.
[0006] For example, when used for closure of vascular punctures,
these devices deploy within a tissue tract to place a suture loop
through tissue on opposite sides of the vascular puncture. Two free
ends of the suture loop are brought out through the tissue tract.
The loops are externally tied by the attending physician, forming a
sliding knot in the suture loop. A tool, called a "knot pusher," is
deployed through the tissue tract for cinching the slidable knot
over the loop. When used to suture vessel punctures, the knot
pusher advances the knot through the tissue tract to locate the
knot over the adventitial wall of the blood vessel, resulting in
puncture edge apposition.
[0007] Despite the skill and due care involved in placing, tying,
and tightening a suture knot using these devices, seepage of blood
and fluids at the suture site and into the tissue tract can still
occur. Under these circumstances, a "dry" femoral closure cannot be
achieved. Hematoma formation can result, which can prolong a
patient's return to ambulatory status without pain and
immobilization.
[0008] Thus, there remains a need for fast and straightforward
systems and methods to achieve suture closure through a tissue
tract, which are substantially free of blood or fluid leakage about
the suture site and into the tissue tract.
SUMMARY OF THE INVENTION
[0009] One aspect of the invention provides systems and methods for
sealing a suture knot. The systems and methods form a suture knot
and discharge a liquid closure material adjacent the suture knot.
The liquid closure material reacts after discharge to form a solid
closure adjacent the suture knot. In one embodiment, a knot pusher
is used to form the suture knot, and the liquid closure material is
discharged through the knot pusher.
[0010] The systems and methods can be used for sealing a puncture
site in a blood vessel.
[0011] Another aspect of the invention provides a knot pusher
comprising a body including a passage having a distal end. The body
is sized and configured to engage a suture knot adjacent the distal
end of the passage. A fitting is carried by body. The fitting is
sized and configured for introducing a liquid closure material into
the passage for discharge through the distal end adjacent the
suture knot. The liquid closure material reacts after discharge to
form a solid closure adjacent the suture knot.
[0012] In one embodiment, the body of the knot pusher is sized and
configured for locating the suture knot in a tissue puncture
tract.
[0013] In one embodiment, the body of the knot pusher is sized and
configured for locating the suture knot adjacent a puncture site in
a blood vessel.
[0014] Another aspect of the invention provides an assembly for
sealing a puncture site in a blood vessel. The assembly comprises a
suture knot formed at the puncture site, and a dispenser to
discharge a liquid closure material adjacent the suture knot. The
liquid closure material reacts after discharge to form a solid
closure adjacent the suture knot.
[0015] In one embodiment, the liquid closure material comprises a
first component including an electrophilic polymer material having
a functionality of at least three; a second component including a
nucleophilic material that, when mixed with the first component and
after discharge as a liquid, cross-links with the first component
to form the solid closure, a non-liquid, three-dimensional barrier;
and a buffer material mixed with the second component. The first
component can include a multi-armed polymer structure, such as,
e.g., poly(ethylene glycol), poly(ethylene oxide), poly(vinyl
alcohol), poly(vinylpyrrolidinone), poly(ethyloxazoline), and
poly(ethylene glycol)-co-poly(propylene glycol) block copolymers.
The second component can include hydrophilic protein, such as,
e.g., serum, serum fractions, solutions of albumin, gelatin,
antibodies, fibrinogen, serum proteins, and recombinant or natural
human serum albumin. The buffer material can include, e.g.,
tris-hydroxymethylaminomethane and/or sodium carbonate
anhydrous.
DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 is a plane view of a system of functional
instruments, with portions broken away and in section, for the
closure of incisions and wounds using a suture knot in combination
with a biocompatible material composition, the system including a
knot pusher and a component introducer/mixer assembly.
[0017] FIG. 2 is a side view of the knot pusher that forms a part
of the system shown in FIG. 1.
[0018] FIG. 3 is a side section view of the knot pusher that forms
a part of the system shown in FIG. 1.
[0019] FIG. 4 is a side view of a mixing element, which forms a
part of the system shown in FIG. 1, coupled for use to the knot
pusher shown in FIGS. 2 and 3.
[0020] FIGS. 5 to 11 illustrate the use of the formative component
assembly, that forms a part of the system shown in FIG. 1, to
deliver a closure composition to the knot pusher shown in FIGS. 2
and 3, wherein FIGS. 5 and 6 are perspective views illustrating the
insertion of the vial component of the formative component
assembly; FIG. 7 is a perspective view illustrating the insertion
of the syringe component of the formative component assembly; FIG.
8 is a side section view illustrating the coupling the assembled
formative component assembly to the mixer element, which, in turn,
is coupled to the knot pusher shown in FIGS. 2 and 3; FIG. 9 is a
side section view illustrating the advancement of the syringe
plunger component of the formative component assembly and further
illustrating the transfer of the liquid component in the syringe
into the vial containing the solid component mixture of the liquid
and the reconstituted solid components in the vial; FIG. 10 is a
side section view illustrating the urging of the mixture from the
vial through the second needle component of the formative component
assembly and into the mixer element; and FIG. 11 is a side section
view illustrating the syringe and vial after the mixture has been
transferred from the vial to the mixer element.
[0021] FIG. 12 is a plane view of a system of functional
instruments for the closure of incisions and wounds using a suture
knot in combination with a biocompatible material composition, the
system including a knot pusher as generally shown in FIGS. 2 and 3
and an alternative embodiment of component introducer/mixer
assembly comprising two syringes coupled to a holder.
[0022] FIG. 13 is a plane exploded view of the component
introducer/mixer assembly shown in FIG. 12, with one of the
syringes withdrawn from the holder.
[0023] FIG. 14 is an assembled view of the component
introducer/mixer assembly shown in FIG. 13.
[0024] FIG. 15 is a plane view of the component introducer/mixer
assembly shown in FIG. 12 coupled for use to the knot pusher shown
in FIGS. 2 and 3.
[0025] FIG. 16 is a diagrammatic view of blood vessel puncture site
formed to enable the delivery of a diagnostic or therapeutic
instrument through a vascular sheath, after removal of the
diagnostic or thereapeutic instrument and the placement of a suture
loop through the puncture site.
[0026] FIG. 17 is a diagrammatic view of the blood vessel puncture
site shown in FIG. 16, after formation of a slidable knot in the
suture loop.
[0027] FIG. 18 is a diagrammatic view of the blood vessel puncture
site shown in FIG. 17, showing the threading of suture in the knot
pusher after formation of the slidable knot.
[0028] FIG. 19 is a diagrammatic view of the blood vessel puncture
site shown in FIG. 18, after threading of suture in the knot pusher
and as the knot pusher is advanced toward the tissue tract, pushing
the slidable knot.
[0029] FIGS. 20 and 21 are diagrammatic views of the blood vessel
puncture site shown in FIG. 19, as the knot pusher is advanced
through the tissue tract to form a suture closure at the vessel
puncture site.
[0030] FIGS. 22 and 23 are diagrammatic views of the blood vessel
puncture site shown in FIGS. 20 and 21, as a closure composition is
being delivered through the knot pusher to envelope the suture
closure and fill the tissue tract.
[0031] FIG. 24 is a diagrammatic view of the blood vessel puncture
site shown in FIGS. 222 and 23, after removal of knot pusher and
after the closure composition has formed a barrier to seal the
suture closure and tissue tract.
[0032] FIG. 25 is a side view, with portions broken away and in
section showing an alternative embodiment of a knot pusher usable
in association with the system shown in FIG. 1, the knot pusher
including an outer sheath and a knot pushing element capable of
being inserted coaxially through the outer sheath.
[0033] FIG. 26 is a diagrammatic view of blood vessel puncture site
formed to enable the delivery of a diagnostic or therapeutic
instrument through a vascular sheath, after removal of the
diagnostic or thereapeutic instrument and the formation of a
slidable knot in a suture loop placed through the puncture site,
and as a suture is being threaded in the knot pusher shown in FIG.
25.
[0034] FIG. 27 is a diagrammatic view of the blood vessel puncture
site shown in FIG. 26, after threading of suture in the knot pusher
and as the knot pusher is advanced toward the tissue tract, pushing
the slidable knot.
[0035] FIG. 28 is a diagrammatic view of the blood vessel puncture
site shown in FIG. 27, as the knot pusher is advanced through the
tissue tract to form a suture closure at the vessel puncture
site.
[0036] FIGS. 29 and 30 are diagrammatic views of the blood vessel
puncture site shown in FIG. 28, as a closure composition is being
delivered through the knot pusher to envelope the suture closure
and fill the tissue tract.
[0037] FIG. 31 is a section view of the knot pusher shown in FIG.
26, taken generally along line 31-31 in FIG. 26 with the knot
pushing element coaxially advanced through the outer sheath and
forming between them a passage through which the closure
composition is delivered to envelope the suture closure and fill
the tissue tract, as FIGS. 29 and 30 show.
DETAILED DESCRIPTION
[0038] Although the disclosure hereof is detailed and exact to
enable those skilled in the art to practice the invention, the
physical embodiments herein disclosed merely exemplify the
invention that may be embodied in other specific structure. While
the preferred embodiment has been described, the details may be
changed without departing from the invention, which is defined by
the claims.
[0039] The systems and methods disclosed herein are shown in the
particular context of closing a vascular puncture site. That is
because the systems and methods are well suited for use in this
indication, and this indication thus provides a representative
embodiment for purposes of description. Still, it should be
appreciated that the systems and methods described can, with
appropriate modification (if necessary), be used for diverse other
indications as well, and in conjunction with delivery mechanisms
that are not necessarily catheter-based. For example, the systems
and methods can be used with delivery mechanisms which use
cannulas, e.g., for the purpose of filling tissue voids or
aneurysms, or for tissue augmentation. As yet another example, the
systems and methods can be used to deliver drug or cells to
targeted locations.
[0040] I. System Overview
[0041] FIG. 1 shows a system 10 of functional instruments for the
closure of incisions and wounds using a suture knot in combination
with a biocompatible material composition. The system 10 is well
suited for use, for example, at a vascular puncture site following
a vascular access procedure.
[0042] As arranged in FIG. 1, the system 10 includes a knot pusher
12 and a component introducer/mixer assembly 30.
[0043] In use (as will be described in greater detail later), the
knot pusher 12 is sized and configured to be manually deployed
during the course of a surgical procedure where a suture loop has
been formed in tissue, to close an incision or wound, or for any
other purpose. In such procedures, a slidable knot is formed in the
suture loop, and the knot pusher 12 is used to engage and advance
the knot to close the loop.
[0044] Also in use (as will be described in greater detail later),
the component introducer/mixer assembly 30 is sized and configured
during the course of such surgical procedures, to be coupled to the
knot pusher 12 to introduce a biocompatible material composition
through the knot pusher 12 into contact with the suture knot in
situ. The biocompatible material composition produces a solid,
three dimensional matrix about the suture knot. The matrix prevents
seepage or leakage of blood and fluids in the area of the suture
knot.
[0045] The system 10 thereby makes possible, through a combination
of suturing, augmented by the deposit of a biocompatible matrix
material, a dry suture closure, which is substantially free of
blood or fluid leakage.
[0046] A. The Knot Pusher
[0047] As shown in FIGS. 1 to 3, the knot pusher comprises an
elongated body or shaft 14. In the illustrated embodiment, the
shaft 14 is sized and configured for passage through a
transcutaneous tissue tract to a vessel puncture site. As shown in
FIG. 16, the tissue track 34 typically will have been previously
formed by a vascular introducer or cannula, through which a desired
therapeutic or diagnostic instrument is first introduced through a
puncture site 36 into the vessel, e.g., to perform coronary
angioplasty. After performing the intended procedure, the
therapeutic or diagnostic instrument and introducer are withdrawn,
leaving the puncture site 36 and the tissue track 34.
[0048] For use in this indication, the shaft 14 will typically have
a length in the range from about 7 cm to 10 cm. Furthermore, for
use in this indication, the outside diameter of the shaft 14 is
desirably sized to seal the tissue track 34 through which it is
introduced (see FIG. 21), so that its presence is hemostatic. In
this context, the outside diameter of the shaft 14 is desirably
selected to match the outside diameter of the vascular introducer,
e.g., from 6 Fr. to 10 Fr, so that the shaft 14, when deployed,
will block substantial flow of blood and fluid from the puncture
site 36 up the tissue track 34 (as shown in FIGS. 20 and 21).
[0049] As shown in FIG. 3, an interior passage 20 extends through
the shaft 14. One end of the passage 20 exits the distal end 16 of
the shaft 14. A side wall slot 22 formed on the distal end 16 opens
into the passage 20.
[0050] In this arrangement, the knot pusher 12 includes a suture
threading fixture 24. The fixture 24 is releasably carried by the
distal end 16 of the shaft 14 in alignment with with the slot 22.
The fixture 24 includes a threader 26. The threader 26 desirably
comprises a loop of thin, flexible wire that is initially
positioned so as to pass through the slot 22, into the passage 20,
and out the distal end 16 of the shaft 14.
[0051] The fixture 24 (see FIGS. 18 and 19) is configured to thread
suture S1 through the passage 20 and slot 22 and thereby engage and
advance a slidable knot 18 in the tissue tract 34 (see FIG. 20).
The slidable knot 18 will have been previously formed (see FIGS. 16
and 17) in a suture loop 20 placed at the puncture site 36, e.g.,
using a device described in U.S. Pat. No. 5,417,699 or U.S. Pat.
No. 5,527,322, which are both incorporated herein by reference. As
FIGS. 16 and 17 show, the slidable knot 18 is formed after
formation of the suture loop 52 by tying the two free ends S1 and
S2 of suture forming the loop 52.
[0052] More particularly, after the slidable knot 18 is formed, the
threading fixture 24 threads a free end S1 through the passage 20
and slot 22 of the knot pusher 12. Using the treading fixture 24,
the attending physician captures a free end S1 of the suture within
the loop of the threader 26 (FIG. 18). The physician disconnects
the fixture 24 from the shaft 14, and pulls the fixture 24 distally
to draw the threader 26 and, with it, the free end S1 of the suture
through the distal shaft end 16 into the passage 20, and then
through the slot 22 (FIG. 19). Upon releasing the free end S4 of
the suture from the threader 26, and discarding the fixture 24, the
physician can then urge the knot pusher 12 through the tissue tract
34, while holding the free suture end S1, to advance and tighten
the slidable knot 18 within the tissue tract 34, as FIGS. 20 and 21
show. The knot pusher 12 engages and advances the slidable knot 18
over the free end S1 of the suture, to close the loop 20 and bring
the edges of the puncture site 36 into apposition. The slidable
knot 18 can then be tightened by pulling on the other free end S2
of the suture, forming a suture closure 28 (shown in FIG. 21).
[0053] B. The Component Introducer/Mixer Assembly
[0054] Upon forming the suture closure 28 using the knot pusher 12
in the manner just described, the component introducer/mixer
assembly 30 is assembled and coupled to the knot pusher 12 (see
FIG. 22). In use (see FIGS. 22 and 23), the assembly 30 places a
biocompatible material composition 50 about the suture closure 28
outside the blood vessel and, desirably, at least partially up the
tissue tract 34 from the puncture site 36. Most desirably, at the
end of the procedure, the composition 50 fills the tissue tract 34,
as FIG. 24 shows. The biocompatible material composition 50
desirably produces a solid, three dimensional matrix that prevents
seepage of blood and fluids through the suture closure 28 and up
the tissue tract 34. The system 10 thereby creates a dry closure,
which is substantially free of blood or fluid leakage about the
suture closure 28 and in the tissue tract 34.
[0055] The biocompatible material composition 50 can take various
forms. Desirably, the biocompatible material composition 50 is
comprised of two or more formative components which are mixed by
the assembly 30 and introduced in a liquid state through the knot
pusher 12 transcutaneously to the suture closure 28. Upon mixing,
the formative components react, in a process called "gelation," to
transform in situ from the liquid state, to a semi-solid (gel)
state, and then to the biocompatible solid state.
[0056] In the solid state, the composition 50 takes the form of a
non-liquid, three-dimensional network. Desirably, the solid
material composition 50 exhibits strength (adhering it to adjacent
tissue), cohesive strength (forming a mechanical barrier that is
resistant to blood pressure and blood seepage), and elasticity
(accommodating the normal stresses and strains of everyday
activity). These properties alone can provide an effective closure
to the vascular puncture site, without use of a suture closure 28.
However, when used with a suture closure 28, the properties of the
composition 50 serve to significantly enhance and augment the
localized closure properties of the suture itself.
[0057] The solid material composition 50 is also capable of
transforming over time by physiological mechanisms from the solid
state to a biocompatible liquid state, which can be cleared by the
body, in a process called "degradation."
[0058] The components forming the material composition 50 can vary.
Generally speaking, however, the components will include a solid
component and a liquid component, which serves as a diluent for the
solid component. Mixing of these two components initiates a
chemical reaction, by which the liquid mixture transforms into a
solid composition.
[0059] A port 32 on the knot pusher 12 (see FIGS. 1 to 3)
communicates with proximal end of the passage 20. The port 32
permits coupling of the component introducer/mixer assembly 30 to
the knot pusher 12 (see FIG. 22).
[0060] The assembly 30 itself can be variously constructed. In the
embodiment shown in FIG. 1, the introducer/mixer assembly 30
includes a mixing assembly 38 and a formative component assembly
40. It is the purpose of the mixing assembly 38 and the formative
component assembly 40 to facilitate the mixing of components for
delivery through the knot pusher 12 to the suture closure 28.
[0061] (i) The Mixing Element
[0062] The mixing assembly 38 (see FIGS. 1 and 4) couples at one
end to the port 32 of the knot pusher 12, to thereby establish
communication with the interior passage 20. The other end of the
mixing assembly 38 includes a luer fitting 42 that, in use, couples
to the formative component assembly 40 (see FIG. 8), to thereby
establish communication between the assembly 40 and the interior
passage 20 through the mixing assembly 38.
[0063] In the illustrated embodiment (as best shown in FIG. 1), the
mixing assembly 38 includes, in the direction of flow from the
formative component assembly 40 toward the passage 20, an in-line
syringe activated check valve 44, an in-line mixer 46, and an
in-line air accumulator 48.
[0064] The in-line syringe activated check valve 44 can take
various forms. In the illustrated embodiment, the valve 44 takes
the form of a conventional, needleless slip luer lock valve made by
Qosina (Edgewood, N.Y.), Product Number 80360. The valve 44 is
normally closed to prevent back flow of blood or other liquid
material through the assembly 38. Back flow of blood, in
particular, from the passage 20 toward the formative component
assembly 40 is undesirable, because it creates the potential for
blood contact and deposits material that can interfere or compete
with the desired reaction between the liquid components that form
the material composition. Connection of a conventional luer fitting
carried by the formative component assembly 38 (for example,
fitting 132 shown in FIGS. 1 and 9) opens the valve 44 to allow the
introduction of the liquid components that form the material
composition.
[0065] The components of the material composition come into
intimate mixing contact in the liquid state in the inline mixer 46.
In this way, effective mixing can be achieved outside the knot
pusher 12. Thus, mixing is not entirely dependent upon the
dimensions or lengths of the flow paths within the knot pusher 12.
The mixer 46 comprises a mixing structure, which can vary. For
example, the mixer 46 can comprise a spiral mixer manufactured by
TAH Industries, Inc. (Robbinsville, N.J.), Part Number
121-090-08.
[0066] The in-line air accumulator 48 comprises a chamber that has
an interior volume sized to trap air that can reside in the
material composition applicator at time of use.
[0067] (ii) The Formative Component Assembly
[0068] In the illustrated embodiment (see FIGS. 1 and 8), the
formative component assembly 40 comprises a unitary applicator 92
in which a vial 94 holding a solid component 96 and a syringe 98
holding a liquid component 100 can be placed and kept separate in
interior compartments.
[0069] Axial advancement of the syringe plunger 102 (see FIG. 9)
propels the liquid 100 into the vial 94 and brings the two
components 96 and 100 together within the vial 94 by placing the
solid component 96 into suspension within the liquid component 100.
The force created by this process also urges the liquid suspension
into the mixing assembly 38 for further mixing and delivery through
the knot pusher passage 20.
[0070] The applicator 92 includes a partition 104 (see FIG. 1) that
divides the applicator 92 into a first compartment 106 and a second
compartment 108, each having an open end 110. The first compartment
106 is sized and configured to receive and hold the vial 94. The
first compartment 106 includes a flanged end region 112 that serves
to support the applicator 92 in an upright position (e.g., standing
on a table). The flanged region 112 further serves to receive a cap
114, as will be described in greater detail later. The second
compartment 108 is sized and configured to receive and hold the
syringe 98. The applicator 92 can be made of any suitable inert,
rigid plastic or metal material. In a representative embodiment,
the first compartment 106 is, e.g., 21/2 inches long, the second
compartment 108 is 2 inches long, and the applicator 92 is 1 inch
high. This arrangement readily accommodates a conventional vial 94
and a conventional syringe 98.
[0071] The syringe 98 can be a conventional syringe 98 having a
plunger 102. The dispensing end 116 includes a luer fitting 118.
The syringe 98 is aseptically pre-filled with the liquid component
100 and a cap 119 is placed over the dispensing end 116 to prevent
leakage and evaporation of the contents.
[0072] As FIG. 1 shows, a first needle 120 extends along the
central line axis of the applicator 92 and couples the syringe 98
to the vial 94 via a luer fitting 122 that mates with the luer
fitting 118 on the syringe 98 (also see FIG. 7). The needle 120
thereby provides communication between the first and second
compartments 106 and 108. Desirably, the needle 120 includes a
plurality of side holes 1hat serve to uniformly introduce the
contents of the syringe 98 into the vial 94 (see FIG. 9).
[0073] As FIG. 1 shows, a second needle 126 is offset from the
central line axis of the applicator 92 and serves to couple the
vial 94 to a molded passage 128 that traverses the wall of the
second compartment 108. The molded passage 128 is coupled to the
proximal end of a length of flexible tubing 130. The distal end of
the tubing 130 includes a luer fitting 132 adapted to couple to the
luer fitting 42 on the mixing assembly 38, as already described.
his arrangement provides fluid communication between the vial 94
and the mixing assembly 38. Optionally, an in-line air vent 131
(shown in phantom lines in FIG. 1), made, e.g., from a sintered
plastic material, can be located in the tubing 130, or otherwise
placed in communication with the tubing 130, to allow residual air
to vent from fluid prior to entering the mixing assembly 38.
[0074] The vial 94 is a conventional pharmaceutical vial 94 sized
to hold the solid component 96 and a pre-defined volume of the
liquid component 100, i.e., the volume of liquid component 100
pre-filled in the syringe 98. The vial 94 includes a septum 134
configured to be pierced and penetrated by the needles 120 and 126
when the vial 94 is properly positioned within the first
compartment 106.
[0075] To aid in positioning and securing of the vial 94 within the
compartment 106, the applicator 92 includes a selectively removable
cap 114, as previously noted. The cap 114 mates with the applicator
92, e.g., by snap-fit engagement with the flanged region 112 on the
applicator 92. Desirably (see FIG. 6), the cap 114 extends into the
first compartment 106 to position and hold the vial 94 in a desired
position after the septum 134 has been pierced by the needles 120
and 126.
[0076] In use (see FIGS. 5 and 6), the physician (or assistant)
removes the cap 114 from the applicator 92. As seen in FIG. 5, with
the cap 114 removed, the physician slides the first compartment 106
over the vial 94. During this step, the vial 94 can be placed on a
counter, table, or other flat support surface. As seen in FIG. 6,
the cap 114 is then placed beneath the vial 94 (e.g., on the
counter or table), and the physician continues to slide the first
compartment 106 over the vial 94, to finish piercing the vial
septum 134 with the needles 120 and 126 and locating the vial 94
fully into the first compartment 106. The cap 114 thereafter holds
the vial 94 in this position.
[0077] As shown in FIG. 7, the cap 119 is then removed from the
syringe 98 and residual air is expressed from the syringe 98, e.g.,
by holding the syringe 98 with the dispensing end 116 upright and
gently tapping the syringe 98 until essentially all of the residual
air rises to the dispensing end 116 and then advancing the plunger
102 until the air is expelled (not shown).
[0078] As FIG. 7 shows, the syringe 98 is then placed within the
second compartment 108 and rotated (represented by an arrow) to
couple the syringe 98 to the first needle 120 through luer fittings
118 and 122. With the syringe 98 and vial 94 in place within the
applicator 92 and the formative assembly 40 ready for use, as seen
in FIG. 8, the assembly 40 can then be coupled to the mixing
assembly 38 (shown in phantom lines) by coupling (represented by
arrows) luer fittings 42 and 132.
[0079] As will be apparent, alternatively, the syringe 98 can be
coupled to the first needle 120 prior to the vial 94 being placed
in the first compartment 106.
[0080] With reference now to FIG. 9, the formative component
assembly 40 is then placed in an upright position (i.e., vial
septum 134 pointing upward and dispensing end 116 of the syringe 98
pointing downward). The plunger 102 is then advanced (represented
by an arrow) to transfer the contents of the syringe 98 through the
first needle 120 into the vial 94. If desired, the assembly 18 can
be stood on a counter, table, or other flat surface as the plunger
102 is advanced. Alternatively, the plunger 102 can be advanced in
conventional fashion by the thumb of the physician while the
syringe 98, with attached applicator 92, are held between the
forefinger and middle finger, as FIG. 9 shows.
[0081] The propulsion of the liquid component 100 into the vial 94
reconstitutes the solid component 96, mixes the components 96 and
100 (represented by arrows in FIG. 9), and begins the reaction
process.
[0082] Fluid pressure created by operation of the syringe 98 urges
the mixture into and through the second needle 126, into the mixing
38, as indicated by arrows in FIG. 10. The mixing assembly 38
further mixes the mixture and rids the fluid path of residual air,
as previously described. The mixture flows through the mixing
assembly 38 and through the knot pusher passage 20. The mixture
exits the knot pusher 12 through the distal end 16, as FIG. 22
shows.
[0083] With reference now to FIG. 11, the plunger 102 is advanced
until essentially all of the liquid component 100 is transferred
from the syringe 98 to the vial 94. Generally concurrently, the
mixture is transferred from the vial 94 into the mixing assembly
38, with only minimal residual mixture remaining in the vial 94. As
will apparent to one skilled in the art, the volume of components
96 and 100 are calculated to account for this residual volume.
[0084] Further details of the component introducer/mixer assembly
30 just described are disclosed in copending U.S. patent
application Ser. No. 10/141,510, filed May 8, 2002 and entitled
"Systems, Methods, and Compositions for Achieving Closure of
Vascular Puncture Sites," which is incorporated herein by
reference.
[0085] Alternatively (see FIGS. 12 to 15), the formative component
assembly 40 can comprise individual syringes 54 and 56 in which the
components are separately contained. The syringes 54 and 56 are, in
use, coupled to a holder 58. In use, the holder 58 is coupled via a
luer fitting 59 to the mixer element 38, as FIG. 15 shows. Further
details of this arrangement are disclosed in copending U.S. patent
application Ser. No. 09/187,384, filed Nov. 6, 1998 and entitled
"Systems and Methods for Applying Cross-Linked Mechanical
Barriers," which is incorporated herein by reference.
[0086] (iii) The Material Composition
[0087] The components 96 and 100 of the material composition can
vary. In a preferred embodiment, the solid component 96 comprises
an electrophilic (electrode withdrawing) material having a
functionality of at least three. The liquid component 100 comprises
a solution containing a nucleophilic (electron donator) material
and a buffer. When mixed under proper reaction conditions, the
electrophilic material and buffered nucleophilic material react, by
cross-linking with each other. The cross-linking of the components
form the composition. The composition physically forms a mechanical
barrier (see FIG. 24), which can also be characterized as a
hydrogel.
[0088] The type and concentration of a buffer material controls the
pH of the liquid and solid components 100 and 96, when brought into
contact for mixing. The buffer material desirably establishes an
initial pH in numeric terms, as well regulates change of the pH
over time.
The Electrophilic Component
[0089] In its most preferred form, the electrophilic (electrode
withdrawing) material 96 comprises a hydrophilic, biocompatible
polymer that is electrophilically derivatized with a functionality
of at least three. Examples include poly(ethylene glycol),
poly(ethylene oxide), poly(vinyl alcohol),
poly(vinylpyrrolidinone), poly(ethyloxazoline), and poly(ethylene
glycol)-co-poly(propylene glycol) block copolymers.
[0090] As used herein, a polymer meeting the above criteria is one
that begins with a multiple arm core (e.g., pentaerythritol) and
not a bifunctional starting material, and which is synthesized to a
desired molecular weight (by derivatizing the end groups), such
that polymers with functional groups greater than or equal to three
constitute (according to gel permeation chromatography--GPC) at
least 50% or more of the polymer blend.
[0091] The material 96 is not restricted to synthetic polymers, as
polysaccharides, carbohydrates, and proteins could be
electrophilically derivatized with a functionality of at least
three. In addition, hybrid proteins with one or more substitutions,
deletions, or additions in the primary structure may be used as the
material 96. In this arrangement, the protein's primary structure
is not restricted to those found in nature, as an amino acid
sequence can be synthetically designed to achieve a particular
structure and/or function and then incorporated into the material.
The protein of the polymer material 96 can be recombinantly
produced or collected from naturally occurring sources.
[0092] Preferably, the polymer material 96 is comprised of
poly(ethylene glycol) (PEG) with a molecular weight preferably
between 9,000 and 12,000, and most preferably 10,500.+-.1500. PEG
has been demonstrated to be biocompatible and non-toxic in a
variety of physiological applications. The preferred concentrations
of the polymer are 5% to 35% w/w, more preferably 5% to 20% w/w.
The polymer can be dissolved in a variety of solutions, but sterile
water is preferred.
[0093] The most preferred polymer material 96 can be generally
expressed as compounds of the formula:
PEG-(DCR-CG).sub.n
[0094] Where:
[0095] DCR is a degradation control region.
[0096] CG is a cross-linking group.
[0097] n.gtoreq.3
[0098] The electrophilic CG is responsible for the cross-linking of
the preferred nucleophilic material 96, as well as binding the
composition 136 to the like material in the surrounding tissue, as
will be described later. The CG can be selected to selectively
react with thiols, selectively react with amines, or react with
thiols and amines. CG's that are selective to thiols include vinyl
sulfone, N-ethyl maleimide, iodoacetamide, and orthopyridyl
disulfide. CG's that are selective to amines include aldehydes.
Non-selective electrophilic groups include active esters, epoxides,
oxycarbonylimidazole, nitrophenyl carbonates, tresylate, mesylate,
tosylate, and isocyanate. The preferred CG's are active esters,
more preferred, an ester of N-hydroxysuccinimide. The active esters
are preferred since they react rapidly with nucleophilic groups and
have a non-toxic leaving group, e.g., hydroxysuccinimide.
[0099] The concentration of the CG in the polymer material 96 can
be used to control the rate of gelation. However, changes in this
concentration typically also result in changes in the desired
mechanical properties of the hydrogel.
[0100] The rate of degradation is controlled by the degradation
control region (DCR), the concentration of the CG's in the polymer
solution, and the concentration of the nucleophilic groups in the
protein solution. Changes in these concentrations also typically
result in changes in the mechanical properties of the hydrogel, as
well as the rate of degradation.
[0101] The rate of degradation (which desirably occurs in about 30
days) is best controlled by the selection of the chemical moiety in
the degradation control region, DCR. If degradation is not desired,
a DCR can be selected to prevent biodegradation or the material can
be created without a DCR. However, if degradation is desired, a
hydrolytically or enzymatically degradable DCR can be selected.
Examples of hydrolytically degradable moieties include saturated
di-acids, unsaturated di-acids, poly(glycolic acid), poly(DL-lactic
acid), poly(L-lactic acid),poly(.xi.-caprolactone),
poly(.delta.-valerolactone),poly(.gamma.-b- utyrolactone),
poly(amino acids),poly(anhydrides), poly(orthoesters),
poly(orthocarbonates), and poly(phosphoesters), and derivatives
thereof. A preferred hydrolytically degradable DCR is gluturate.
Examples of enzymatically degradable DCR's include Leu-Gly-Pro-Ala
(collagenase sensitive linkage) and Gly-Pro-Lys (plasmin sensitive
linkage). It should also be appreciated that the DCR could contain
combinations of degradable groups, e.g. poly(glycolic acid) and
di-acid.
[0102] While the preferred polymer is a multi-armed structure, a
linear polymer with a functionality, or reactive groups per
molecule, of at least three can also be used. The utility of a
given PEG polymer significantly increases when the functionality is
increased to be greater than or equal to three. The observed
incremental increase in functionality occurs when the functionality
is increased from two to three, and again when the functionality is
increased from three to four. Further incremental increases are
minimal when the functionality exceeds about four.
[0103] A preferred polymer may be purchased from SunBio Company
((PEG-SG).sub.4, having a molecular weight of 10,500.+-.1500)(which
will sometimes be called the "SunBio PEG").
The Nucleophilic Component
[0104] In a most preferred embodiment, the nucleophilic material
100 includes non-immunogenic, hydrophilic proteins. Examples
include serum, serum fractions, and solutions of albumin, gelatin,
antibodies, fibrinogen, and serum proteins. In addition, water
soluble derivatives of hydrophobic proteins can be used. Examples
include solutions of collagen, elastin, chitosan, and hyaluronic
acid. In addition, hybrid proteins with one or more substitutions,
deletions, or additions in the primary structure may be used.
[0105] Furthermore, the primary protein structure need not be
restricted to those found in nature. An amino acid sequence can be
synthetically designed to achieve a particular structure and/or
function and then incorporated into the nucleophilic material 100.
The protein can be recombinantly produced or collected from
naturally occurring sources.
[0106] The preferred protein solution is 25% human serum albumin,
USP. Human serum albumin is preferred due to its biocompatibility
and its ready availability.
[0107] The uses of PEG polymers with functionality of greater than
three provides a surprising advantage when albumin is used as the
nucleophilic material 100. When cross-linked with higher
functionality PEG polymers, the concentration of albumin can be
reduced to 25% and below. Past uses of difunctional PEG polymers
require concentrations of albumin well above 25%, e.g. 35% to 45%.
Use of lower concentrations of albumin result in superior tissue
sealing properties with increased elasticity, a further desired
result. Additionally, 25% human serum albumin, USP is commercially
available from several sources, however higher concentrations of
human serum albumin, USP are not commercially available. By using
commercially available materials, the dialysis and ultrafiltration
of the albumin solution, as disclosed in the prior art, is
eliminated, significantly reducing the cost and complexity of the
preparation of the albumin solution.
[0108] To minimize the liberation of heat during the cross-linking
reaction, the concentration of the cross-linking groups of the
fundamental polymer component is preferably kept less than 5% of
the total mass of the reactive solution, and more preferably about
1% or less. The low concentration of the cross-linking group is
also beneficial so that the amount of the leaving group is also
minimized. In a typical clinical application, about 50 mg of a
non-toxic leaving group is produced during the cross-linking
reaction, a further desired result. In a preferred embodiment, the
CG comprising an N-hydroxysuccinimide ester has demonstrated
ability to participate in the cross-linking reaction with albumin
without eliciting adverse immune responses in humans.
The Buffer Component
[0109] In the most preferred embodiment, a PEG reactive ester
reacts with the amino groups of the albumin and other tissue
proteins, with the release of N-hydroxysuccinimide and the
formation of a link between the PEG and the protein. When there are
multiple reactive ester groups per PEG molecule, and each protein
has many reactive groups, a network of links form, binding all the
albumin molecules to each other and to adjacent tissue
proteins.
[0110] This reaction with protein amino groups is not the only
reaction that the PEG reactive ester can undergo. It can also react
with water (i.e., hydrolyze), thereby losing its ability to react
with protein. For this reason, the PEG reactive ester must be
stored dry before use and dissolved under conditions where it does
not hydrolyze rapidly. The storage container for the PEG material
desirably is evacuated by use of a vacuum, and the PEG material is
stored therein under an inert gas, such as Argon or Nitrogen.
Another method of packaging the PEG material is to lyophilize the
PEG material and store it under vacuum, or under an inert gas, such
as Argon or Nitrogen, as will be described in greater detail later.
Lyophilization provides the benefits of long term storage and
product stability, as well as allows rapid dissolution of the PEG
material in water.
[0111] The conditions that speed up hydrolysis tend to parallel
those that speed up the reaction with protein; namely, increased
temperature; increased concentration; and increased pH (i.e.,
increased alkali). In the illustrated embodiment, temperature
cannot be easily varied, so varying the concentrations and the pH
are the primary methods of control.
[0112] It has been discovered, through bench testing, that when
cross-linking the SunBio PEG with albumin (Plasbumin), a range of
gelation times between an acceptable moderate time (about 30
seconds) to a rapid time (about 2 seconds) can be achieved by
establishing a pH range from about 8 (the moderate times) to about
10 (the rapid times). Ascertaining the cross-linking pH range aids
in the selection of buffer materials from among phosphate,
tris-hydroxymethylaminomethane (Tris), and carbonate, which are all
non-toxic, biocompatible buffers.
[0113] Further details of the material composition are found in
copending U.S. patent application Ser. No. 09/780,014, filed Feb.
9, 2001, and entitled "Systems, Methods, and Compositions for
Achieving Closure of Vascular Puncture Sites," which is
incorporated herein by reference.
Representative Embodiment
[0114] In a representative embodiment employed with a 7 FR device,
the vial 94 contains 600 mg.+-.10% of lyophilized SunBio PEG-SG
(4-arm polyethylene glycol tetrasuccinimidyl glutarate--MW
10,500.+-.1500). Details of the lyophilization process are
described in U.S. patent application Ser. No. 10/141,510, filed May
8, 2002 and entitled "Systems, Methods, and Compositions for
Achieving Closure of Vascular Puncture Sites," which is
incorporated herein by reference. The syringe 98 contains 6 ml of
water and 2 ml of buffered 25% w/w human serum albumin, USP. The
buffered 25% albumin is made by adding 0.217 g. of
Tris-hydroxymethlaminomethane (C.sub.4H.sub.11NO.sub.3) (FW 121.1)
(TRIS Buffer) to 20 cc of Bayer Plasbumin.RTM. -25 to obtain a pH
between 8.0 and 8.7, most preferably between 8.3 and 8.5.
[0115] II. Representative Use of the System
[0116] Use of the knot pusher 12 in conventional fashion will form
the suture closure 28, as FIGS. 16 to 21 show. As FIG. 22 shows,
once coupled to the knot pusher 12, operation of the formative
component assembly 40, as previously described, expresses the
components 96 and 100, while in liquid form, through the mixer
element 38 and through the knot pusher 12. The gelating components
50 flow out the distal end 16 and slot 22 of the knot pusher and
into the subcutaneous tissue surrounding the suture closure 28.
[0117] The knot pusher 12 is desirably sized to seal the tissue
track 34, to block substantial flow in a path up the tissue track
34. Thus, the gelating components 50 are first delivered in a
liquid state adjacent to the suture closure 28. The incoming flow,
directed in this manner, creates a tissue space about the suture
closure 28. The gelating components 50 fill this space. Desirably
(see FIG. 23), after first introducing the gelating components 50
at the site of the suture closure 28, the physician slowly
withdraws the knot pusher 12 up the tissue tract 34 while still
delivering the components 50, to substantially fill the entire
tissue tract 34 with the gelating components 50.
[0118] In the gelation process, the electrophilic component and the
nucleophilic component cross-link, and the developing composition
50 gains cohesive strength to close the suture closure 28 and the
tissue tract 34. The electrophilic component also begins to
cross-link with nucleophilic groups on the surrounding tissue
mass.
[0119] Adhesive strength forms, which begins to adhere the
developing composition to the surrounding tissue mass.
[0120] During the introduction stage, before internal cohesive and
tissue adhesive strengths fully develop, a portion of the gelating
components 50 can seep through the suture closure 28 and enter the
blood vessel. Upon entering the blood stream, the gelating
components 50 will immediately experience physical dilution. The
dilution expands the distance between the electrophilic component
and the nucleophilic component, making crosslinking difficult. In
addition, the diluted components now experience an environment
having a pH (7.3 to 7.4) lower than the an effective reactive pH
for cross-linking (which is above 8) (as an example, a typical
gelation time at pH 8.3 is about 15 to 20 seconds, whereas a
typical gelation time at pH 7.4 is over 10 minutes). As a result,
incidence of cross-linking within the blood vessel, to form the
hydrogel composition, is only a fraction of what it is outside the
vessel, where gelation continues.
[0121] Furthermore, the diluted electrophilic component will absorb
nucleophilic proteins present in the blood. This reaction further
reduces the reactivity of the electrophilic component. In blood,
the diluted electrophilic component is transformed into a
biocompatible, non-reactive entity, which can be readily cleared by
the kidneys and excreted. The diluted nucleophilic component 100 is
a naturally occurring protein that is handled in normal ways by the
body.
[0122] This stage preferably last about 5 to 30 seconds from the
time the physician begins to mix the components 96 and 100.
[0123] A second stage begins after the physician has delivered the
entire prescribed volume of components 96 and 100 to the tissue
mass of the suture closure 28 and tissue tract 34. At this point,
the cross-linking of the components 96 and 100 has progressed to
the point where a semi-solid gel occupies the formed tissue space.
The physician can now applies localized and temporary compression
to the exterior skin surface surrounding the tissue track 34.
[0124] The application of localized pressure serves two purposes.
It is not to prevent blood flow through the tissue track 34, as
cross-linking of the components 96 and 100 has already proceeded to
create a semi-solid gel having sufficient cohesive and adhesive
strength to impede blood flow from the puncture site. Rather, the
localized pressure serves to compress the tissue mass about the
semi-solid gel mass. This compression brings the semi-solid gel
mass into intimate contact with surrounding tissue mass, while the
final stages of cross-linking and gelation take place.
[0125] Under localized compression pressure, any remnant track of
the knot pusher 12 existing through the gel mass will also be
closed.
[0126] Under localized compression pressure, surface contact
between the adhesive gel mass and tissue is also increased, to
promote the cross-linking reaction with nucleophilic groups in the
surrounding tissue mass. Adhesive strength between the gel mass and
tissue is thereby allowed to fully develop, to firmly adhere the
gel mass to the surrounding tissue as the solid composition 50
forms in situ.
[0127] During this stage, blood will also contact the vessel-side,
exposed portion of the gel mass, which now covers the tissue
puncture site. The electrophilic component will absorb nucleophilic
proteins present in the blood, forming a biocompatible surface on
the inside of the vessel.
[0128] The second stage preferably last about 3 to 10 minutes from
the time the physician withdraws the knot pusher 12. At the end of
the second stage, the solid composition 50 has formed (as FIG. 24
shows). Hemostasis has been achieved. The suture ends S1 and S2 can
be trimmed at the skin surface, and the individual is free to
ambulate and quickly return to normal day-to-day functions.
[0129] The mechanical properties of the solid composition 50 are
such to form a mechanical barrier. The composition 50 is well
tolerated by the body, without invoking a severe foreign body
response. Over a controlled period, the material composition 50 is
degraded by physiological mechanisms. As the material is degraded,
the tissue returns to a quiescent state. The molecules of the
degraded genus hydrogel composition are cleared from the
bloodstream by the kidneys and eliminated from the body in the
urine. In a preferred embodiment of the invention, the material
loses its physical strength during the first fifteen days, and
totally resorbs in about four to eight weeks, depending upon the
person's body mass.
[0130] III. Alternative Embodiment
[0131] FIG. 25 shows an alternative embodiment of a knot pusher 60
for the closure of incisions and wounds using a suture knot in
combination with a biocompatible material composition. Like the
knot pusher 12, the knot pusher 60 is well suited for use, for
example, at a vascular puncture site following a vascular access
procedure. In use (see FIGS. 29 and 30), like the knot pusher 12,
the knot pusher 60 accommodates coupling to a component
introducer/mixer assembly 30 of the type shown in either FIG. 1 or
FIG. 15, to introduce a biocompatible material composition to the
site of a suture closure 28 through a transcutaneous tissue tract
34. In FIGS. 29 and 30, an assembly 30 of the type shown in FIG. 15
is shown for purposes of illustration.
[0132] In the embodiment shown in FIG. 25, the knot pusher 60
comprises a coaxial assembly of an outer sheath 62 and an inner
knot pushing element 64. A lumen 66 in the outer sheath 62
accommodates passage of the knot pushing element 64, as FIG. 26
shows. The lumen 66 includes an open distal end 76 and a port 78 at
the proximal end, to which the assembly 30 is coupled during use
(as shown in FIG. 29). In this arrangement (see FIG. 31), a passage
68 is formed between the exterior of the knot pushing element 64
and the interior wall of the lumen 66. The port 78 and open distal
end 76 communicate with the passage 68. As will be described later,
it is through this passage 68 that the material composition 50 is
introduced.
[0133] Like the knot pusher 12, the knot pusher 60 comprises an
elongated body or shaft 70 having a distal end 72. The shaft 14 is
sized and configured for passage through the lumen 66 of the outer
sheath. It is also sized and configured, when passed through the
lumen 66, to have its distal end 72 extend beyond the open distal
end 76 of the outer sheath 62, as FIG. 26 shows.
[0134] Unlike the knot pusher 12, the knot pusher 60 does not
include a through-passage to conduct the biocompatible material
composition 50. Instead, in use, the biocompatible material
composition is conducted through the passage 68 that is formed
between the knot pushing element 64 and the interior wall of the
lumen 66.
[0135] The knot pusher 60 includes a suture threading fixture 24 of
the type previously described in association with the knot pusher
12. The fixture 24 can be releasably carried by the distal end 72
of the shaft 70 in alignment with a slotted passage 74 in the
distal end 72 of the shaft 70.
[0136] The fixture 24 likewise includes a threader 26 of a type
previously described. As before described, the threader 26
desirably comprises a loop of thin, flexible wire that is initially
positioned so as to pass through the slotted passage 74 and out the
distal end 72 of the shaft 70.
[0137] In use, with the fixture 24 unattached, the knot pushing
element 64 is passed through the lumen 66 of outer sheath 62. The
threader 26 can then be passed through the slotted passage 74,
which is exposed beyond the distal end 76 of the outer sheath 62.
If desired, the fixture 24 can also be releasably secured to the
distal end 72 of the knot pushing element 64 (as FIG. 26
shows).
[0138] After the slidable knot 18 is formed (as previously
described), the attending physician captures a free end S1 of the
suture within the loop of the threader 26 (as FIG. 27 shows).
Freeing the fixture 24 from the distal end 72, the physician pulls
the fixture 24 distally to draw the threader 26 and, with it, the
free end S1 of the suture through the slotted passage 74. Upon
releasing the free end S1 of the suture from the threader 26, and
discarding the fixture 24, the physician can then urge the knot
pushing element64 and the outer sheath 62 as an assembled unit
through the tissue tract 34 (as FIG. 28 shows). Holding the free
suture end S1, the physician advances the assembled knot pusher 60
to tighten the slidable knot 18 within the tissue tract 34, as FIG.
28 shows. The knot pusher 60 engages and advances the slidable knot
18 over the free end S1 of the suture, to close the suture loop 20
and bring the edges of the puncture site 36 into apposition. The
slidable knot 18 can then be tightened by pulling on the other free
end S2 of the suture, forming a suture closure 28 (shown in FIG.
28). In this arrangement, the suture end S1 serves as a guide wire,
to locate and guide the assembled knot pusher 60 generally over the
center of the suture closure 28.
[0139] Upon forming the suture closure 28 using the knot pusher 60
in the manner just described, the component introducer/mixer
assembly 30 can be assembled and coupled to the port 78 of the
outer sheath 62(see FIG. 29). The assembly 30 is manipulated in the
manner previously described to introduce a biocompatible material
composition 50 through the passage 68 and out the open distal end
76 of the outer sheath 62. The composition 50 is placed about the
suture closure 28 outside the blood vessel. Desirably (see FIG.
30), by simultaneously withdrawing the knot pusher 60 up the tissue
tract 34 as the composition 50 is conducted out the open distal end
76, the composition 50 can also be placed in at least portion of
the tissue tract 34. Most desirably (as FIG. 30 shows), at the end
of the procedure, the composition 50 fills the tissue tract 34.
[0140] As already described, the biocompatible material composition
50 desirably produces a solid, three dimensional matrix that
prevents seepage of blood and fluids through the suture closure 28
and up the tissue tract 34. The knot pusher 60 thereby creates a
dry closure, which is substantially free of blood or fluid leakage
about the suture closure 28 and in the tissue tract 34.
[0141] The foregoing is considered as illustrative only of the
principles of the invention. Furthermore, since numerous
modifications and changes will readily occur to those skilled in
the art, it is not desired to limit the invention to the exact
construction and operation shown and described. While the preferred
embodiment has been described, the details may be changed without
departing from the invention, which is defined by the claims.
* * * * *